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71.
Shuhei Fukuno Katsuhito Nagai Kohei Yamamoto Takehiro Tanimura Takeshi Nabe Hiroki Konishi 《Biopharmaceutics & drug disposition》2019,40(7):225-233
The study examined the effect of doxorubicin (DOX) on the hepatic expression of CYP2C and its activity for metabolizing tolbutamide (TB), a specific CYP2C substrate, in rats and whether the pharmacokinetics of tolbutamide were altered by doxorubicin exposure. The expression level of hepatic CYP2C11 was depressed 1 day after doxorubicin administration (day 1), and this effect on CYP2C11 was augmented on day 4. However, the expression level of hepatic CYP2C6 remained unchanged. The activity of tolbutamide 4‐hydroxylation in hepatic microsomes was decreased with time following doxorubicin administration. Regarding the enzyme kinetic parameters for tolbutamide 4‐hydroxylation on day 4, the maximum velocity (Vmax) was significantly lower in the DOX group than that in the control group, while the Michaelis constant (Km) was unaffected. On pharmacokinetic examination, the total clearance (CLtot) of tolbutamide on day 4 was increased, despite the decreased metabolic capacity. On the other hand, the serum unbound fraction (fu) of tolbutamide was elevated with a reduced serum albumin concentration in the DOX group. Contrary to CLtot, CLtot/fu, a parameter approximated to the hepatic intrinsic clearance of unbound tolbutamide, was estimated to be significantly reduced in the DOX group. These findings indicate that the metabolic capacity of CYP2C11 in the liver is depressed time‐dependently by down‐regulation after doxorubicin exposure in rats, and that the decreased enzyme activity of TB 4‐hydroxylation in hepatic microsomes reflects the pharmacokinetic change of unbound tolbutamide, not total tolbutamide, in serum. 相似文献
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Masanori Atsukawa Akihito Tsubota Hidenori Toyoda Koichi Takaguchi Makoto Nakamuta Tsunamasa Watanabe Kojiro Michitaka Tadashi Ikegami Akito Nozaki Haruki Uojima Shinya Fukunishi Takuya Genda Hiroshi Abe Naoki Hotta Kunihiko Tsuji Chikara Ogawa Yoshihiko Tachi Toshihide Shima Noritomo Shimada Chisa Kondo Takehiro Akahane Yoshio Aizawa Yasuhito Tanaka Takashi Kumada Katsuhiko Iwakiri 《Alimentary pharmacology & therapeutics》2019,49(9):1230-1241
74.
Nobuyasu Awano Nene Oyama Keiko Akiyama Minoru Inomata Naoyuki Kuse Mari Tone Kohei Takada Yutaka Muto Kazushi Fujimoto Yu Akagi Momoko Mawatari Akihiro Ueda Junko Kawakami Junko Komatsu Takehiro Izumo 《Internal medicine (Tokyo, Japan)》2020,59(21):2693
Objective Coronavirus disease 2019 (COVID-19) is spreading around the world. The aim of this study was to assess the degree of anxiety, depression, resilience, and other psychiatric symptoms among healthcare workers in Japan during the COVID-19 pandemic. Methods This survey involved medical healthcare workers at the Japanese Red Cross Medical Center (Tokyo, Japan) between April 22 and May 15, 2020. The degree of symptoms of anxiety, depression, and resilience was assessed using the Japanese versions of the 7-item Generalized Anxiety Disorder Scale (GAD-7), Center for Epidemiologic Studies Depression Scale (CES-D), and 10-item Connor-Davidson Resilience Scale. Furthermore, we added original questionnaires comprising three factors: (i) anxiety and fear of infection and death; (ii) isolation and unreasonable treatment; and (iii) motivation and escape behavior at work. Results In total, 848 healthcare workers participated in this survey: 104 doctors, 461 nurses, 184 other co-medical staff, and 99 office workers. Among all participants, 85 (10.0%) developed moderate-to-severe anxiety disorder, and 237 (27.9%) developed depression. Problems with anxiety and fear of infection and death, isolation and unreasonable treatment, and motivation and escape from work were higher in the depression group than in the non-depression group (total CES-D score ≥ 16 points). Being a nurse and high total GAD-7 scores were risk factors of depression. Older workers and those with higher resilience were less likely to develop depression than others. Conclusion During the COVID-19 epidemic, many healthcare workers suffered from psychiatric symptoms. Psychological support and interventions for protecting the mental health of them are needed. 相似文献
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Daichi Fujimoto Hiroyuki Ueda Ryoko Shimizu Ryoji Kato Takehiro Otoshi Takahisa Kawamura Koji Tamai Yumi Shibata Takeshi Matsumoto Kazuma Nagata Kyoko Otsuka Atsushi Nakagawa Kojiro Otsuka Nobuyuki Katakami Keisuke Tomii 《Clinical & experimental metastasis》2014,31(5):543-551
Mutated epidermal growth factor receptor (EGFR) and signaling pathways were associated with multiple brain and intra-pulmonary metastases, oncogenic progression and metastasis. However, features of metastasis to other organs and the independent prognostic influence of metastatic lesions were not elucidated in patients with lung cancer harboring EGFR mutations. Between January 2007 and April 2012, we treated 277 patients diagnosed with stage IV lung adenocarcinoma. Studied were 246 patients with available tumor EGFR mutation data who also underwent radiographic evaluation of lung, abdominal, brain, and bone metastases. The EGFR mutated group (N = 98) had significantly more metastatic lesions in the brain and bone than the wild-type group (N = 148): brain, 3 (1–93) versus 2 (1–32) median (range), P = 0.023; bone, 3 (1–43) versus 2 (1–27), P = 0.035, respectively. In addition, EGFR mutations were significantly more frequent in patients with multiple than non-multiple lung metastases (24/40 vs. 12/42, P = 0.004). Multivariate analysis showed that bone metastasis was a significant independent negative predictive factor of overall survival (OS) in patients with mutated [hazard ratio (HR) 2.04; 95 % confidence interval (CI) 1.17–3.64; P = 0.011] and wild-type EGFR (HR 2.09; 95 % CI 1.37–3.20; P < 0.001). In conclusion, patients with mutated EGFR had more lung, brain, and bone metastases, and bone metastasis was an independent negative predictor of OS. 相似文献
77.
Prenatal molecular diagnosis of X‐linked hydrocephalus via a silent C924T mutation in the L1CAM gene
Takehiro Serikawa Kenichi Nishiyama Jun Tohyama Ryushi Tazawa Kiyoe Goto Yoko Kuriyama Kazufumi Haino Yonehiro Kanemura Mami Yamasaki Koh Nakata Koichi Takakuwa Takayuki Enomoto 《Congenital anomalies》2014,54(4):243-245
We present a case of a patient whose L1CAM gene in X‐chromosome has a C924T transition. Her first son's ventriculomegaly was prenatally detected. A mature infant was born, his head circumference was large, and thumbs were bilaterally adducted. X‐linked hydrocephalus (XLH) was suspected. The DNA examination revealed that both her and boy's LICAM gene had a C924T transition. She became pregnant 5 years later and amniocentesis was performed. The results of cytogenetic analysis revealed that the fetus was female. She continued her pregnancy and delivered a healthy girl. She again became pregnant 3 years later. The chromosomal analysis revealed that the fetus was male. Fetal DNA analysis determined that the fetus had the inherited mutation. She chose to terminate the pregnancy. A C924T mutation can be disease causing for XLH, and the detection of this mutation would aid in genetic counseling for the prenatal diagnosis of XLH. 相似文献
78.
Yuta Takeuchi Yuma Ebihara Yoshitsugu Nakanishi Toshimichi Asano Takehiro Noji Yo Kurashima Soichi Murakami Toru Nakamura Takahiro Tsuchikawa Keisuke Okamura Toshiaki Shichinohe Satoshi Hirano 《Asian journal of endoscopic surgery》2020,13(2):215-218
We report a novel technique for combined laparoscopy and thoracoscopy for far‐advanced adenocarcinoma of the esophagogastric junction (AEG). A 56‐year‐old man presented with far‐advanced AEG, and an esophagogastroduodenoscopy revealed a type 2 lesion that encircled the esophagogastric junction. CT revealed stenosis of the esophagogastric junction, suspected invasion into the left side of the diaphragm, and lymph node metastases in the abdomen. We diagnosed Siewert type II AEG (cT4aN1M0, cStage IIIA) according to the Japanese Classification of Gastric Carcinoma, version 14. Laparoscopic and thoracoscopic proximal gastrectomy and lower esophagectomy with double‐tract reconstruction were performed as a palliative resection via a minimally invasive abdominal and left thoracic approach. However, localized peritoneal dissemination was detected. The patient was discharged with no postoperative morbidity. Hence, a minimally invasive abdominal and left thoracic approach provides good visualization, and it is safe for lower esophageal transection and intrathoracic anastomosis in the treatment of locally advanced AEG invading the surrounding tissues. 相似文献
79.
80.
Ryuichi Kita Naoshi Nishida Yoshihiro Fukuda Hidemasa Azechi Yoko Matsuoka Toshiki Komeda Takehiro Sando Kazuwa Nakao Kanji Ishizaki 《International journal of cancer. Journal international du cancer》1996,67(2):176-180
We examined the genomic status of the p16INK4A (inhibitor of cyclin-dependent kinase 4 A) and cyclin-dependent kinase 4 (CDK4) genes in 62 human hepatocellular carcinomas (HCCs), 5 cholangiocellular carcinomas and 6 cell lines derived from human liver cancers. Although no samples showed the homozygous deletion of the p16INK4A gene, we detected intragenic mutations of the p16INK4A gene in 3 HCCs and one HCC cell line, which led to an amino-acid substitution or a frameshift. In 2 HCC samples with mis-sense mutations of the p16INK4A gene, loss of heterozygosity on 9p22 was also detected, suggesting that the loss of function of p16 was induced during hepatocarcinogenesis. On the other hand, amplification or rearrangement of the CDK4 gene was not detected in any samples examined in this study. These results indicated that the mutations or deletions of the p16INK4A gene are not frequent, but may play a role in a sub-set of human HCC. © 1996 Wiley-Liss, Inc. 相似文献